Atherosclerosis is a complex arterial disease which occurs at a earlier age and with greater morbidity and mortality in people with diabetes mellitus than in the general population. Unfortunately there are very few animal models which have both diseases and a major objective of this proposal is to produce and study atherosclerosis in two new animal models, the obese/hyperglycemic PBB/Ld mouse and spontaneously diabetic NZW rabbit. Two additional models will be explored. These are the African green monkey and dog, which will develop severe atherosclerosis when fed diets containing saturated fat and cholesterol. Diabetes will be produced in these two species by infusion of streptozotocin into the pancreas. Factorial experiments will be conducted and analysis of variance of data will be utilized to detect and measure main effect(s) and interaction of diabetes, saturated fat, essential fatty acids, cholesterol and ascorbic acid in production of atherosclerosis. Intravenous glucose tolerance and plasma lipoprotein distribution and composition (cholesterol and triglyceride) will be determined at intervals throughout 12 to 18 month experiments. At termination of studies necropsies will be performed, and systematic microscopic analysis of aorta, heart, coronary and other arteries using hematoxylin and eosin and several special stains will be done by two observers.